The purpose of the project is to develop new experimental models for an approach to the immunotherapy of cancer, which appears to hold considerable promise, but which has not yet been tested systematically in the clinic. This approach is adoptive immunotherapy with lymphoid cells that have been sensitized against neoplastic cells in vitro (effector cells), amplified in number by means of TCGF, and applied therapeutically in conjunction with other regimens (surgery, chemo/ radiotherapy, bone marrow transplantation). Procedures have been developed for effective in vitro sensitization (mixed lymphocyte-tumor cell culture, MLTC) of spleen and lymph node lymphocytes from normal and tumor-bearing mice against poorly immunogenic, radiation-induced lymphomas and spontaneous lung and mammary carcinomas. Several means employed to augment the elicitation of antitumor cytotoxic responses are: depletion of suppressor cells from responder cell populations, addition of TCGF to the sensitization cultures and use of normal allogeneic leukocytes as stimulator cells instead of tumor cells. Cells of cultures showing marked antitumor cytotoxic or proliferative activity were separated into subpopulations on density gradients. The separated lymphoblast populations were then expanded numerically 103-\to 108-fold over a period of 3 to 8 weeks by culture in TCGF. Such cells are now being cloned. In preliminary chemoadoptive immunotherapy experiments in mice with advanced neoplastic disease, the sensitized propagated effector cells exhibited considerable therapeutic effect when given repeatedly, and in conjunction with chemotherapeutic agents and TCGF. Other combined therapeutic measures will be included in upcoming experiments.